In order to study the glucagon sensitive adenylate cyclase system of liver membranes while maintaining its functional integrity, we have successfully utilized a reversible cross-linking reagent to maintain the multimolecular components of the complex as an active oligomeric assembly. We have obtained an adenylate cyclase preparation that maintains its glucagon activated state after exposure of liver membranes to the hormone and to cross-linking reagents. We plan to exploit this experimental finding and to isolate the coupled receptor-enzyme complex as a cross-linked system from membranes and to uncouple the isolated complex so as to analyze the components therein. The cross-linked complex can be isolated from other membrane components, after solubilization of membranes with detergents, by gradient sedimentation techniques or by anion exchange or gel filtration chromatography. The isolated oligomeric assembly of the coupled hormone activated enzyme will be subjected to cross-linking reversal and the products examined. By these means, we expect to characterize the hormone receptor, the coupling components that are involved in coupling the receptor to the enzyme after the binding of the hormone to the receptor, the guanyl nucleotide binding protein, and the catalytic unit that is involved in converting ATP to cyclic AMP. Reconstitution of the hormone sensitive enzyme system in a membrane matrix will be attempted in a manner that has already been utilized in this laboratory for inserting the catalytic component of the liver adenylate cyclase system into red cell membranes.